Indole metabolites and colorectal cancer: Gut microbial tryptophan metabolism, host gut microbiome biomarkers, and potential intervention mechanisms

Liu, Yuanyuan; Pei, Zhangming; Pan, Tong; Wang, Hongchao; Chen, Wei; Liu, Wenwei

doi:10.1016/j.micres.2023.127392

Cited by 10 publications

(10 citation statements)

References 118 publications

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“…Our data demonstrated that CK significantly restored the levels of microbial tryptophan derivatives (indole derivatives, including 5-HTP, IPYA, IPA, and IA) in IBD mice. Tryptophan metabolic pathways could produce IA and IPA, two tryptophan metabolites that are recognized to influence intestinal permeability and host immune responses. ,,− Notably, we identified IA as a crucial indicative metabolite in CK-treated mice. Moreover, we showed that IA could prevent the disruption of the intestinal epithelial barrier, exhibiting similar effects of CK in ameliorating DSS-induced IBD, which suggested that CK may exert its anti-IBD effects through microbial tryptophan metabolites.…”

Section: Discussionmentioning

confidence: 99%

Ginsenoside CK Alleviates DSS-Induced IBD in Mice by Regulating Tryptophan Metabolism and Activating Aryl Hydrocarbon Receptor via Gut Microbiota Modulation

Liu,

Bai,

et al. 2024

J. Agric. Food Chem.

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Dysbiosis of gut microbiota is believed to be associated with inflammatory bowel disease (IBD). Ginsenoside compound K (CK), the main metabolite of Panax ginseng ginsenoside, has proven effective as an anti-inflammatory agent in IBD. However, the mechanisms by which CK modulates gut microbiota to ameliorate IBD remain poorly understood. Herein, CK demonstrated the potential to suppress the release of proinflammatory cytokines by gut microbiota modulation. Notably, supplementation with CK promoted the restoration of a harmonious balance in gut microbiota, primarily by enhancing the populations of Lactobacillus and Akkermansia. Furthermore, CK considerably elevated the concentrations of tryptophan metabolites derived from Lactobacillus that could activate the aryl hydrocarbon receptor. Overall, the promising alleviative efficacy of CK primarily stemmed from the promotion of Lactobacillus growth and production of tryptophan metabolites, suggesting that CK should be regarded as a prospective prebiotic agent for IBD in the future.

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Section: Discussionmentioning

confidence: 99%

Ginsenoside CK Alleviates DSS-Induced IBD in Mice by Regulating Tryptophan Metabolism and Activating Aryl Hydrocarbon Receptor via Gut Microbiota Modulation

Liu,

Bai,

et al. 2024

J. Agric. Food Chem.

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“…Indole is produced from dietary tryptophan by the gut microbiota and enters the body through the intestinal epithelium [ 19 ]. Indole is metabolized in the liver, but the complete metabolic pathway and specific intermediate metabolites are still debated [ 22 , 23 , 31 , 35 ]. Therefore, in this study, we investigated the metabolism of the aromatic heterocyclic compound indole in vivo.…”

Section: Discussionmentioning

confidence: 99%

Unraveling the Dynamics of Host–Microbiota Indole Metabolism: An Investigation of Indole, Indolin-2-one, Isatin, and 3-Hydroxyindolin-2-one

Kunevičius,

Sadauskas,

Raudytė

et al. 2024

Molecules

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The gut microbiota produces a variety of bioactive molecules that facilitate host–microbiota interaction. Indole and its metabolites are focused as possible biomarkers for various diseases. However, data on indole metabolism and individual metabolites remain limited. Hence, we investigated the metabolism and distribution of indole, indolin-2-one, isatin, and 3-hydroxyindolin-2-one. First, we orally administered a high dose of indole into C57BL/6J mice and measured the concentrations of indole metabolites in the brain, liver, plasma, large and small intestines, and cecum at multiple time points using HPLC/MS. Absorption in 30 min and full metabolization in 6 h were established. Furthermore, indole, indolin-2-one, and 3-hydroxiindolin-2-one, but not isatin, were found in the brain. Second, we confirmed these findings by using stable isotope-carrying indole. Third, we identified 3-hydroxyindolin-2-one as an indole metabolite in vivo by utilizing a 3-hydroxyindolin-2-one-converting enzyme, IifA. Further, we confirmed the ability of orally administered 3-hydroxyindolin-2-one to cross the blood–brain barrier in a dose-dependent manner. Finally, we detected upregulation of the CYP1A2 and CYP2A5 genes, confirming the importance of these cytochrome isoforms in indole metabolism in vivo. Overall, our results provide a basic characterization of indole metabolism in the host and highlight 3-hydroxyindolin-2-one as a potentially brain-affecting indole metabolite.

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“…Phenylethylamine is an essential amino acid that is involved in energy metabolism (glucose and fat) and synthesis of certain types of hormones as well as neurotransmitters [ 28 ]. The metabolism of tryptophan is a complex multi-pathway process that involves the host’s intestinal microbiota through symbiotic relationships [ 29 ]. The tryptophan metabolism generates several metabolites as a coproduct of these pathways, and these coproducts strengthen the immune function of the animal [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

Effects of Dietary Protein Levels on Sheep Gut Metabolite Profiles during the Lactating Stage

Ali,

Ni,

Khan

et al. 2023

Animals

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Diet-associated characteristics such as dietary protein levels can modulate the gut’s primary or secondary metabolites, leading to effects on the productive performance and overall health of animals. Whereas fecal metabolite changes are closely associated with gut metabolome, this study aimed to see changes in the rumen metabolite profile of lactating ewes fed different dietary protein levels. For this, eighteen lactating ewes (approximately 2 years old, averaging 38.52 ± 1.57 kg in their initial body weight) were divided into three groups (n = 6 ewes/group) by following the complete randomized design, and each group was assigned to one of three low-protein (D_I), medium-protein (D_m), and high-protein (D_h) diets containing 8.58%, 10.34%, and 13.93% crude protein contents on a dry basis, respectively. The fecal samples were subjected to untargeted metabolomics using ultra-performance liquid chromatography (UPLC). The metabolomes of the sheep fed to the high-protein-diet group were distinguished as per principal-component analysis from the medium- and low-protein diets. Fecal metabolite concentrations as well as their patterns were changed by feeding different dietary protein levels. The discriminating metabolites between groups of nursing sheep fed different protein levels were identified using partial least-squares discriminant analysis. The pathway enrichment revealed that dietary protein levels mainly influenced the metabolism-associated pathways (n = 63 and 39 in positive as well as negative ionic modes, respectively) followed by protein (n = 15 and 8 in positive as well as negative ionic modes, respectively) and amino-acid (n = 14 and 7 in positive as well as negative ionic modes, respectively) synthesis. Multivariate and univariate analyses showed comparative changes in the fecal concentrations of metabolites in both positive and negative ionic modes. Major changes were observed in protein metabolism, organic-acid biosynthesis, and fatty-acid oxidation. Pairwise analysis and PCA reveal a higher degree of aggregation within the D-h group than all other pairs. In both the PCA and PLS-DA plots, the comparative separation among the D_h/D_m, D_h/D_I, and D_m/D_I groups was superior in positive as well as negative ionic modes, which indicated that sheep fed higher protein levels had alterations in the levels of the metabolites. These metabolic findings provide insights into potentiated biomarker changes in the metabolism influenced by dietary protein levels. The target identification may further increase our knowledge of sheep gut metabolome, particularly regarding how dietary protein levels influence the molecular mechanisms of nutritional metabolism, growth performance, and milk synthesis of sheep.

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Indole metabolites and colorectal cancer: Gut microbial tryptophan metabolism, host gut microbiome biomarkers, and potential intervention mechanisms

Cited by 10 publications

References 118 publications

Ginsenoside CK Alleviates DSS-Induced IBD in Mice by Regulating Tryptophan Metabolism and Activating Aryl Hydrocarbon Receptor via Gut Microbiota Modulation

Ginsenoside CK Alleviates DSS-Induced IBD in Mice by Regulating Tryptophan Metabolism and Activating Aryl Hydrocarbon Receptor via Gut Microbiota Modulation

Unraveling the Dynamics of Host–Microbiota Indole Metabolism: An Investigation of Indole, Indolin-2-one, Isatin, and 3-Hydroxyindolin-2-one

Effects of Dietary Protein Levels on Sheep Gut Metabolite Profiles during the Lactating Stage

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